title: Uptake, metabolism and toxicity of hemin in cultured neurons.
abstract: Following hemorrhagic stroke, red blood cells lyse and release neurotoxic hemin into the interstitial space. The present study investigates whether neurons can accumulate and metabolize hemin. We demonstrate that cultured neurons express the heme carrier protein 1 (HCP1), and that this transporter appears to contribute to the time- and concentration-dependent accumulation of hemin by neurons. Although exposure of neurons to hemin stimulates the synthesis of the iron storage protein ferritin, approximately 80% of the hemin accumulated by neurons remains intact. Within 24h of incubation, substantial neurotoxicity was observed that was not attenuated by the cell permeable, selective ferrous iron chelator, 1,10-phenanthroline. These results demonstrate that while neurons efficiently accumulate hemin they slowly degrade it, and they support the conclusion that intact hemin is more neurotoxic than the iron released from the breakdown of hemin. Further investigations are required to determine the basis of this neurotoxicity.
authors.affiliation: Blood-Brain Interactions Group, School of Psychology and Psychiatry, Monash University, Wellington Road, Clayton, VIC 3800, Australia. theresa.n.dang@gmail.com
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Dang
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Robinson
authors.forename: Ralf
authors.initials: R
authors.lastname: Dringen
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Bishop
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006427:Hemin / Q000378:metabolism* / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006427:Hemin